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To elucidate its spatiotemporal dynamics, we integrated single\u2010nucleus RNA sequencing and spatial transcriptomics to construct a comprehensive aging atlas of 12 human ovarian tissues spanning ages 12\u201354 (prepubertal, age 12,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091; young, ages 23\u201329,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094; middle\u2010aged, ages 32\u201334,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092; and older\u2010aged, ages 42\u201354,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095). Our analysis revealed aging\u2010related transcriptomic shifts, including impaired mitochondrial oxidative phosphorylation and reproductive structure development in aged human ovaries. We identified a novel endothelial cell (EDC) subtype,\n                    <jats:italic>CLDN5<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    blood EDCs, which exhibited unique functional specialization as semiprofessional antigen\u2010presenting cells. In contrast to other cell types that lost cell identity during aging,\n                    <jats:italic>CLDN5<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    blood EDCs displayed transcriptomic sensitivity to aging, characterized by enhanced antigen\u2010presenting capabilities, and heightened inflammatory activity. Spatial mapping further uncovered immunoglobulin\u2010expressing (\n                    <jats:italic>IGHG1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    \/\n                    <jats:italic>IGKC<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    ) cell accumulation in the ovarian periphery, correlating with advancing age. Critically, aging disrupted global cellular connectivity while amplifying the\n                    <jats:italic>DLK1:NOTCH3<\/jats:italic>\n                    axis between theca cells and\n                    <jats:italic>CLDN5<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    blood EDCs, which may contribute to the dysregulation of ovarian functions. We also detected the upregulation of\n                    <jats:italic>DLK1<\/jats:italic>\n                    in granulosa cells from patients with primary ovarian insufficiency. This study significantly enhances our comprehension of the underlying mechanisms of human ovarian aging and concurrently pinpoints potential therapeutic avenues for addressing related disorders.\n                  <\/jats:p>","DOI":"10.1111\/acel.70288","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:17:49Z","timestamp":1763367469000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Spatial Transcriptomic Characteristics of the Aging Human Ovary"],"prefix":"10.1111","volume":"25","author":[{"given":"Meiling","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine &amp; Fertility Preservation Program, International Peace Maternity and Child Health Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Disease  Shanghai 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